Recent progress in the field of glycoconjugates (original) (raw)
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Synthesis of Glycoconjugates in Potentiating Pharmacological and Pharmaceutical Activity
IntechOpen eBooks, 2023
The full range of glycoconjugates made up of glycans, or carbohydrate chains, that are covalently joined to lipid or protein molecules is known as the glycome. Glycoconjugates are created, through the process of glycosylation (vary in length, glycan sequence, and the connections that connect them). The creation of therapies can now take advantage of new knowledge about the structure and operation of the glycome, which may enhance our capacity to control inflammation and immune responses, maximize the efficacy of therapeutic antibodies, and enhance immune responses to cancer. These instances highlight the promise of the young discipline of "glycomedicine." The prevalence of glycoconjugates in nature and their significance in various biological processes have prompted the development of numerous synthesizing techniques for these molecules. Today, synthetic glycoconjugates are utilized to address a wide range of biological concerns linked to glycoconjugates. This study seeks to update earlier reviews on the topic as well as gather and compile the most recent developments in the fields of glycopeptide, glycoprotein, and glycolipid synthesis. Finally, we hope that this study may stimulate fruitful research in this significant area of medicinal chemistry by highlighting the triumphs and shortcomings of prior research.
Glycopeptide/Glycoprotein Synthesis
Protein glycosylation has dramatically enriched both the functional and structural diversity of proteins in mammals. Due to the non-template biosynthesis of glycoproteins in the nature, glyco-proteins always exist as heterogeneous mixtures with different glycan structures, which have complicated the isolation of pure and well-defined glycoforms for detailed mechanistic and functional studies. Over the past years, different strategies including chemical and chemoenzymatic methods have been developed for obtaining the homogenous glycoproteins, which will offer new opportunities to conduct an extensive assessment of relationship between the structure and function of glycoproteins and to reveal the biological role of the individual oligosaccharide on a glycoprotein for the evolution and development of cells. This chapter gives insight into the recent progress in the development of chemical and chemoenzymatic synthesis of homogenous glycoproteins including native chemical ligation, serine/threonine ligation, and chemoenzymatic glycoprotein remodeling. Examples are selected to demonstrate successful applications of synthetic strategies developed so far.
REVIEW Glycopeptides as versatile tools for glycobiology
2006
This review describes the recent advances in the field of glycopeptide and small glycoprotein synthesis. The strategies covered include chemical and chemoenzymatic synthesis, native chemical ligation (NCL), and expressed chemical ligation. The importance of glycopeptide synthesis is exemplified by giving the reader an overview of how versatile and important these well-defined glycopeptides are as tools in glycobiology.
2012
The biological importance of lipopolysaccharides (LPS), components of bacterial cell wall has not been explained sufficiently. The glycine present in these structures could play an important role in the immunological response after bacterial infections and during sepsis. In our studies we obtained synthetic and stable substituted glycinated 1-thioglycosides derivatives of monosaccharides, e.g., D-glucose or D-galactose as well as disaccharides, e.g., melibiose and lactose. The conditions of acylation reactions were validated and specific products were separated by using chromatography methods. Their structures were confirmed by NMR. These compounds were conjugated with carrier proteins e.g., bovine serum albumin and horse myoglobin. Prior to conjugation proteins were modified with glycidol to create the protein-diol intermediates and subsequent periodate oxidation of the glycol moieties to generate the reactive aldehyde functionalities. Modified and formylated carrier proteins were conjugated with acylated thioglycosides in the presence of sodium cyanoborohydride. Subsequently, the products obtained were analyzed in SDS-PAGE and separated by using HW-55S gelfiltration chromatography. The immunoreactivity of selected glycinated glycoconjugates were studied in ELISA assays with specific anti-aminoacylated glyconjugate antibodies obtained after rabbit immunization with Escherichia coli K12 C600 core oligosaccharide glycine-containing glycoconjugate. The differences in the immunoreactivity of different glycinated 1-thioglycosides were observed. The received glycine-acylated glycoconjugates could mimic the non-sugar substituents localized in various bacterial LPS. These synthetic compounds could be candidates for their use as glycoconjugate vaccines in protection against serious bacterial infections, e.g., sepsis.
Glycopeptides as versatile tools for glycobiology
Glycobiology, 2006
This review describes the recent advances in the field of glycopeptide and small glycoprotein synthesis. The strategies covered include chemical and chemoenzymatic synthesis, native chemical ligation (NCL), and expressed chemical ligation. The importance of glycopeptide synthesis is exemplified by giving the reader an overview of how versatile and important these well-defined glycopeptides are as tools in glycobiology.
Chemical and Chemoenzymatic Synthesis of Glycoproteins for Deciphering Functions
Chemistry & Biology, 2014
This study describes the synthesis of the a-and b-linked N-acetyllactosamine (Galp-b-1,4-GlcNAc; LacNAc) glycosides of threonine (LacNAc-Thr). LacNAc-a-Thr was prepared by direct chemical coupling of a 2-azido-2-deoxy-lactose disaccharide donor to a suitable partially protected threonine unit. In contrast, stepwise chemical generation of b-linked N-acetylglucosamine followed by enzymatic galactosylation to give LacNAc-b-Thr proved effective, whereas use of a 2-azido-2-deoxy-lactose donor in acetonitrile failed to give the desired b-linked disaccharyl glycoside. This study illustrates that it is possible to overcome the inherent stereoselection for 1,2-trans chemical glycosylation with a GlcNAc donor, and that the well-established preference of bovine b-1,4-galactosyltransferase for b-linked acceptor substrates can also be overcome. Using this knowledge, short glycopeptide fragments based on T. cruzi mucin sequences, Thr-Thr-[LacNAcThr]-Thr-Thr-Gly, were synthesised. All LacNAc-based compounds outlined were shown to serve as acceptor substrates for sialylation by T. cruzi trans-sialidase. † The a-glycoside appears to be formed directly, not through equilibration of the b-glycoside. Addition of pure b-glycoside to the reaction mixture did not result in additional a-glycoside formation. straightforward and direct approach to the a-linked GlcNAc-Thr system that, given that there is no need to manipulate C-2 functionality, is competitive with other approaches to such a-linked 2-amino-2-deoxy-glucosides. 30,31 Removal of the benzyl ester and Fmoc groups from protected glyco-amino acids (9) and (10) was performed by standard hydrogenation (10% Pd-C/H 2 ); subsequent removal of the acetate groups was realised in the presence of 1 M NaOMe in MeOH. In this way, 20-30 mg quantities of the completely deprotected glyco-amino acids (3) were obtained (Scheme 1).
O-glycosyl α-amino acids as building blocks for glycopeptide synthesis
Tetrahedron: Asymmetry, 1997
A review of 0-glycosyl a-amino acid structures representing most of the glycosylation sites of known 0-glycoproteins found in nature, their preparation by chemical methods and application as building blocks for either solution or solid-phase synthesis of 0-glycopeptides is presented.